PET Imaging of Serotonin Transporters with 4-[<sup>18</sup>F]-ADAM in a Parkinsonian Rat Model with Porcine Neural Xenografts

Chiu, Chuang-Hsin; Li, I‐Hsun; Weng, Shao-Ju; Huang, Yuahn-Sieh; Wu, Shinn-Chih; Chou, Ta-Kai; Huang, Wen-Sheng; Liao, Mei-Hsiu; Shiue, Chyng‐Yann; Cheng, Cheng‐Yi; Ma, Kuo‐Hsing

doi:10.3727/096368915x688236

Cited by 12 publications

(7 citation statements)

References 72 publications

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“…DA- and 5-HT-depleted rats exhibited attenuated hyperlocomotor activity after treatment with 5-HT2 agonists 80 . However, our previous data showed that serotonin levels are decreased after 6-OHDA treatment 83,84 . In line with our previous findings, Zhang et al showed that the use of a broad-spectrum 5-HT receptor antagonist did not affect the hyperactivity of rats subjected to neonatal 6-OHDA lesioning 64 , suggesting that striatal serotoninergic fibers are not the key player in influencing locomotor activity in rats.…”

Section: Discussionmentioning

confidence: 87%

The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

et al. 2020

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While Parkinson’s disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan’s Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.

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Section: Discussionmentioning

confidence: 87%

The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

et al. 2020

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“…DsRed is expressed ubiquitously, with red fluorescence detected in the brain, eye, tongue, heart, lung, liver, pancreas, spleen, stomach, small intestine, large intestine, kidney, testis, and muscle, as confirmed by histology and western blot analyses. Red fluorescence tracking was previously applied in transplantation of neurons from Ds-Red transgenic pigs into a Parkinson’s disease rat model [55]. In this in vivo experiment, precise evaluation and analysis could be achieved due to the abundant expression of the two fluorescent proteins in all differentiated progeny.…”

Section: Discussionmentioning

confidence: 99%

Bone regeneration in Ds-Red pig calvarial defect using allogenic transplantation of EGFP-pMSCs – A comparison of host cells and seeding cells in the scaffold

Hsieh

et al. 2019

PLoS ONE

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Background Cells, scaffolds, and factors are the triad of regenerative engineering; however, it is difficult to distinguish whether cells in the regenerative construct are from the seeded cells or host cells via the host blood supply. We performed a novel in vivo study to transplant enhanced green fluorescent pig mesenchymal stem cells (EGFP-pMSCs) into calvarial defect of DsRed pigs. The cell distribution and proportion were distinguished by the different fluorescent colors through the whole regenerative period. Method/Results Eight adult domestic Ds-Red pigs were treated with five modalities: empty defects without scaffold (group 1); defects filled only with scaffold (group 2); defects filled with osteoinduction medium-loaded scaffold (group 3); defects filled with 5 x 10 3 cells/scaffold (group 4); and defects filled with 5 x 10 4 cells/scaffold (group 5). The in vitro cell distribution, morphology, osteogenic differentiation, and fluorescence images of groups 4 and 5 were analyzed. Two animals were sacrificed at 1, 2, 3, and 4 weeks after transplantation. The in vivo fluorescence imaging and quantification data showed that EGFP-pMSCs were represented in the scaffolds in groups 4 and 5 throughout the whole regenerative period. A higher seeded cell density resulted in more sustained seeded cells in bone regeneration compared to a lower seeded cell density. Host cells were recruited by seeded cells if enough space was available in the scaffold. Host cells in groups 1 to 3 did not change from the 1st week to 4th week, which indicates that the scaffold without seeded cells cannot recruit host cells even when enough space is available for cell ingrowth. The histological and immunohistochemical data showed that more cells were involved in osteogenesis in scaffolds with seeded cells. Conclusion Our in vivo results showed that more seeded cells recruit more host cells and that both cell types participate in osteogenesis. These results suggest that scaffolds without seeded cells may not be effective in bone transplantation.

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“…The pfVM tissues were collected from the porcine fetus of pregnant Lanyu pigs (Taitung Animal Propagation Station, Livestock Research Institute) 19 based on two previous protocols. 38,39 Briefly, the pregnant Lanyu pigs were anesthetized by Zoletil 50 (2 mg/kg, subcutaneous injection; Virbac) and maintained by 2% isoflurane/ oxygen (Abbott Laboratories Ltd.).…”

Section: Mesencephalic Tissue Preparation and Transplantationmentioning

confidence: 99%

“…pfVM group (n = 6) was grafted with ~2.5 × 10 5 E27 pfVM cells in the striatum. 19,31,40 pfVM + OECs group (n = 6) was grafted with ~ 2.5 × 10 5 E27 pfVM cells and ~2.5 × 10 5 OECs in the lesioned striatum. The grafting tissues were cut into small pieces and then transplanted into the lesioned striatum (0.5 mm posterior to bregma, 2.5 mm lateral to the midline, and 5.5 mm below the dura) using a glass micropipette.…”

Section: F I G U R Ementioning

confidence: 99%

“…18 Transplantation of E27 pfVM and porcine neuroblast cells has also been demonstrated to restore dopaminergic systems in the PD rats. 19,20 Together, pfVM tissues present a potential to be a major donor source for PD cell replacement therapy, and however, host immune response toward the xenograft cells is still a major factor that critically affects the success of xenotransplantation.…”

Section: Introductionmentioning

confidence: 99%

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Olfactory ensheathing cells improve the survival of porcine neural xenografts in a Parkinsonian rat model

Weng

Chen

Huang

et al. 2019

Xenotransplantation

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Background: Parkinson's disease (PD) features the motor control deficits resulting from irreversible, progressive degeneration of dopaminergic (DA) neurons of the nigrostriatal pathway. Although intracerebral transplantation of human fetal ventral mesencephalon (hfVM) has been proven effective at reviving DA function in the PD patients, this treatment is clinically limited by availability of hfVM and the related ethical issues. Homologous tissues to hfVM, such as porcine fetal ventral mesencephalon (pfVM) thus present a strong clinical potential if immune response following xenotransplantation could be tamed. Olfactory ensheathing cells (OECs) are glial cells showing immunomodulatory properties. It is unclear but intriuging whether these properties can be applied to reducing immune response following neural xenotransplantation of PD. Methods: To determine whether OECs may benefit neural xenografts for PD, different compositions of grafting cells were transplanted into striatum of the PD model rats. We used apomorphine-induced rotational behavior to evaluate effectiveness of the neural grafts on reviving DA function. Immunohistochemistry was applied to investigate the effect of OECs on the survival of neuroxenografts and underlying mechanisms of this effect.Results: Four weeks following the xenotransplantation, we found that the PD rats receiving pfVM + OECs co-graft exhibited a better improvement in apomorphine-induced rotational behavior compared with those receiving only pfVM cells. This result can be explained by higher survival of DA neurons (tyrosine hydroxylase immunoreactivity) in grafted striatum of pfVM + OECs group. Furthermore, pfVM + OECs group has less immune response (CD3 + T cells and OX-6 + microglia) around the grafted area compared with pfVM only group. These results suggest that OECs may enhance the survival of the striatal xenografts via dampening the immune response at the grafted sites.

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PET Imaging of Serotonin Transporters with 4-[¹⁸F]-ADAM in a Parkinsonian Rat Model with Porcine Neural Xenografts

Cited by 12 publications

References 72 publications

The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

Bone regeneration in Ds-Red pig calvarial defect using allogenic transplantation of EGFP-pMSCs – A comparison of host cells and seeding cells in the scaffold

Olfactory ensheathing cells improve the survival of porcine neural xenografts in a Parkinsonian rat model

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PET Imaging of Serotonin Transporters with 4-[18F]-ADAM in a Parkinsonian Rat Model with Porcine Neural Xenografts

Cited by 12 publications

References 72 publications

The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

Bone regeneration in Ds-Red pig calvarial defect using allogenic transplantation of EGFP-pMSCs – A comparison of host cells and seeding cells in the scaffold

Olfactory ensheathing cells improve the survival of porcine neural xenografts in a Parkinsonian rat model

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PET Imaging of Serotonin Transporters with 4-[¹⁸F]-ADAM in a Parkinsonian Rat Model with Porcine Neural Xenografts